{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:51:54Z","timestamp":1792144314604,"version":"4.4.0"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Melatonin is recommended as a first\u2010line treatment in isolated REM sleep behavior disorder (iRBD), although no large patient group has been reported. To assess effects, time course and confounding factors in the treatment of patients with iRBD using melatonin, 209 consecutive patients were included in this single\u2010center, observational cohort study. A total of 171 patients had taken melatonin according to our chronobiotic protocol (2\u00a0mg, \u22656\u00a0months,\n                    <jats:italic>always\u2010at\u2010the\u2010same\u2010clock time,<\/jats:italic>\n                    10\u201011pm, corrected for chronotype), 13 had applied melatonin for about 1\u20103\u00a0months, and 25 underwent mixed treatments. In total, 1529 clinical evaluations were performed, including Clinical Global Impression (CGI) and a newly developed RBD symptom severity scale (Ikelos\u2010RS), analyzed using linear mixed models. Validation of Ikelos\u2010RS showed excellent inter\u2010rater reliability (\u03c1\u00a0=\u00a00.9,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a0.001), test\u2010retest reliability (\u03c1\u00a0=\u00a00.9,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a0.001) and convergent validity (\u03c1\u00a0=\u00a00.9,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a0.001). With melatonin, RBD symptom severity gradually improved over the first 4\u00a0weeks of treatment (Ikelos\u2010RS: 6.1 vs. 2.5; CGI Severity: 5.7 vs. 3.2) and remained stably improved (mean follow\u2010up 4.2\u00a0\u00b1\u00a03.1years; range: 0.6\u201021.7years). Initial response was slowed to up to 3\u00a0months with melatonin\u2010suppressing (betablockers) or REM sleep spoiling co\u2010medication (antidepressants) and failed with inadequately timed melatonin intake. When melatonin was discontinued after 6\u00a0months, symptoms remained stably improved (mean follow\u2010up after discontinuation of 4.9\u00a0\u00b1\u00a02.5years; range: 0.6\u20109.2). When administered only 1\u20103\u00a0months, RBD symptoms gradually returned. Without any melatonin, RBD symptoms persisted and did not wear off over time. Clock\u2010timed, low\u2010dose, long\u2010term melatonin treatment in patients with iRBD appears to be associated with the improvement of symptoms. The outlasting improvement over years questions a pure symptomatic effect. Clock\u2010time dependency challenges existing prescription guidelines for melatonin.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12759","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T09:36:52Z","timestamp":1627292212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Treatment of isolated REM sleep behavior disorder using melatonin as a chronobiotic"],"prefix":"10.1111","volume":"71","author":[{"given":"Dieter","family":"Kunz","sequence":"first","affiliation":[{"name":"Clinic for Sleep &amp; Chronomedicine St. Hedwig\u2010Krankenhaus Berlin  Berlin Germany"},{"name":"Institute of Physiology Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Stotz","sequence":"additional","affiliation":[{"name":"Clinic for Sleep &amp; Chronomedicine St. Hedwig\u2010Krankenhaus Berlin  Berlin 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